Higher serum lipocalin 2 is associated with post-stroke depression at discharge.

BACKGROUND AND AIMS: Post-stroke depression (PSD), as one of the common complications after stroke, seriously affects the physical and mental health and functional prognosis of patients. Previous studies have shown that the increase of inflammatory mediators is associated with the occurrence of PSD. Lipocalin 2 (LCN2), as an acute phase protein, is involved in the development of acute ischemic stroke (AIS), and its expression is up-regulated in patients with depression, suggesting that there is a potential correlation between serum LCN2 and depression. The aim of this study was to explore the relationship between serum LCN2 at admission and PSD at discharge. METHODS: A total of 358 AIS patients were retrospectively included. All patients had fasting venous blood taken within 24 h of admission to detect serum LCN2. The patients were evaluated by 17-item Hamilton Depression Scale (HAMD) before discharge. Patients with HAMD score > 7 were diagnosed with PSD. The correlation between serum LCN2 and PSD was tested using binary logistic regression analysis. RESULTS: In our study, 92 (25.7%) patients were diagnosed with PSD at discharge. According to the serum LCN2 value, the patients were divided into three layers (Tertile1 ≤ 105.24ng/ml; Tertile2: 105.24-140.12ng/ml; Tertile3 ≥ 140.12ng/ml), with T1 layer (the lowest levels) as a reference, after adjusting for multiple potential confounding factors, T3 layer (the highest levels) was independently associated with the occurrence of PSD (odds ratio [OR] = 2.639, 95% confidence interval [CI]: 1.317-5.287, P = 0.006). Similar results were found when the serum LCN2 was analyzed as a continuous variable. The optimal cut-off value of serum LCN2 at admission to predict PSD at discharge was 117.60ng/ml, at this threshold, the sensitivity was 77.2%, and the specificity was 53.4%. CONCLUSIONS: High serum LCN2 levels at admission are an independent risk factor for PSD in patients with AIS at discharge.

2-BFI Provides Neuroprotection Against Fluorosis by Stabilizing Endoplasmic Reticulum-Mitochondria Contact Sites and Inhibiting Activation of the NLRP3 Inflammasome.

2-(2-benzofu-ranyl)-2-imidazoline (2-BFI) is a drug that has attracted much attention in recent years. It has a therapeutic effect on brain diseases in animal models such as Alzheimer's disease and cerebral infarction. However, whether 2-BFI affords neuroprotection against the toxicity of fluoride, which can cross the blood-brain barrier and cause neurological dysfunction is not known. We investigated the cell viability and apoptosis of SH-SY5Y cells and primary cultures of cortical neurons exposed to fluoride, and 2-BFI was used to protect both two kinds of cells against the effects of fluoride. We found that 2-BFI can provide neuroprotection on SH-SY5Y cells and primary cultures of cortical neurons upon fluorosis by maintaining the stability of endoplasmic reticulum-mitochondria contact sites and inhibiting activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome. This study may provide a new method for protecting against the neurotoxicity induced by fluoride exposure.

miR-190a-3p Promotes Proliferation and Migration in Glioma Cells via YOD1.

INTRODUCTION: To investigate the function of miR-190a-3p on the proliferation and migration of glioma. METHODS: Twenty glioma samples and 6 normal brain tissue samples were collected. Normal human glial cell line HEB and glioma cell lines were used for the experiments. We then used TargetScan to predict the target genes of miR-190a-3p. Dual-luciferase reporter assay was also used to validate. RESULTS: Combined with dual-luciferase reporter experiment, we finally verified that YOD1 was the aim, and it was low-expressed in glioma. Besides, a series of mechanism experiments then proved that miR-190a-3p negatively regulates YOD1 expression. CONCLUSIONS: Our research was the first to demonstrate the promoting function of miR-190a-3p in the proliferation and migration of glioma and provided new views for the treatment of glioma. miR-190a-3p was expected to be a new target for molecular therapy of glioma.

Sinensetin Attenuates Amyloid Beta25-35-Induced Oxidative Stress, Inflammation, and Apoptosis in SH-SY5Y Cells Through the TLR4/NF-κB Signaling Pathway.

Sinensetin (SIN) is an important active compound that exists widely in citrus plants, and has been reported to exhibit various pharmacological properties, including anti-oxidative, anti-inflammatory, and anti-tumor. This study was designed to examine whether SIN can protect against amyloid beta (Aß)-induced neurotoxicity and to elucidate the underlying mechanism. Our results showed that pretreatment with SIN for 1 h, followed by co-treatment with Aß plus SIN for 24 h, attenuated Aß25-35-induced cell viability reduction, oxidative stress, inflammation, and apoptosis in a dose-dependent manner. Aß25-35-induced upregulation of Toll-like receptor 4 (TLR4) expression and nuclear translocation of nuclear factor-kappaB (NF-κB) p65 subunit were inhibited by pretreatment with SIN. Furthermore, the protective effect of SIN was abrogated by TLR4 overexpression. Hence, our data suggested that SIN attenuated Aß25-35-induced neurotoxicity through the TLR4/NF-κB pathway.

Targeting the TLR4/NF-κB pathway in ß-amyloid-stimulated microglial cells: A possible mechanism that oxysophoridine exerts anti-oxidative and anti-inflammatory effects in an in vitro model of Alzheimer's disease.

ß-amyloid (Aß) accumulation is a major neuropathological characteristic of Alzheimer's disease (AD) and serves as an inflammatory stimulus for microglial cells. Oxysophoridine has multiple pharmacological effects, including anti-inflammatory and anti-oxidative activities. In view of this, the current study aimed to investigate the effects of oxysophoridine on Aß-induced activation of microglial BV-2 cells. Cell Counting Kit-8 assay showed that oxysophoridine concentration-dependently attenuated Aß-induced viability reduction of BV-2 cells. Aß stimulation reduced the activities of glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD) and elevated malondialdehyde (MDA) content in BV-2 cells, but these effects were attenuated by oxysophoridine. Oxysophoridine abolished Aß-induced increase of mRNA expression, secretion, and protein expression of tumor necrosis factor-α (TNF-α) and interleukin 1ß (IL-1ß) in BV-2 cells. Additionally, western blot suggested that oxysophoridine inhibited Aß-induced activation of the toll-like receptor 4 (TLR4) and nuclear factor-kappa B (NF-κB) pathways in BV-2 cells. Inhibition of the TLR4/NF-κB pathway by TAK-242 enhanced the effects of oxysophoridine on Aß-induced viability reduction, oxidative stress, and inflammation in BV-2 cells. Taken together, oxysophoridine suppressed Aß-induced oxidative stress and inflammation in BV-2 cells by inhibition of the TLR4/NF-κB pathway.

Pseudogene ANXA2P2 knockdown shows tumor-suppressive function by inhibition of the PI3K/PKB pathway in glioblastoma cells.

The pseudogene annexin A2 pseudogene 2 (ANXA2P2) is highly expressed in glioblastoma (GBM). However, its role and mechanism involved in the progression of GBM remain poorly understood. ANXA2P2 messenger RNA expression was measured by quantitative reverse transcription-polymerase chain reaction. The protein levels were detected by Western blot. Cell viability was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase (LDH) release assays. Cell invasive ability was investigated by the transwell assay and by epithelial-mesenchymal transition (EMT). Cell apoptosis was examined by flow cytometry. The results showed that ANXA2P2 expression was increased in GBM tissues and cells. Silencing of ANXA2P2 inhibited the activation of the phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB) pathway in GBM cells. Knockdown of ANXA2P2 decreased cell viability, promoted LDH release, suppressed cell invasive ability, and EMT, and induced cell apoptosis in GBM cells. The addition of the PI3K/PKB activator 740Y-P abrogated the effects of ANXA2P2 knockdown on cell viability, LDH release, invasive ability, and apoptosis. In conclusion, knockdown of ANXA2P2 inhibited cell viability and invasion but promoted the apoptotic rate by suppressing the PI3K/PKB pathway in GBM cells. ANXA2P2 may represent a new target for the treatment of GBM.

Engeletin Attenuates Aß1-42-Induced Oxidative Stress and Neuroinflammation by Keap1/Nrf2 Pathway.

Alzheimer's disease (AD) is a serious neuropathologic disease characterized by aggregation of amyloid-ß (Aß) peptide. Aß-mediated oxidative stress and neuroinflammation play crucial role in the development of AD. Engeletin is a flavononol glycoside that possesses anti-inflammatory effect. However, the effects of engeletin on AD have not been investigated. In the present study, we investigated the role of engeletin in AD using an in vitro AD model. Murine microglia BV-2 cells were stimulated with Aß1-42 (5 µM) for 24 h to induce oxidative stress and inflammation. Our results showed that treatment with engeletin suppressed Aß1-42-induced viability reduction and lactate dehydrogenase (LDH) release in BV-2 cells. Engeletin attenuated Aß1-42-induced oxidative stress in BV-2 cells, as proved by decreased production of reactive oxygen species (ROS) and malonaldehyde (MDA) and increased glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities. Aß1-42-induced nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression were inhibited by engeletin treatment. Besides, engeletin inhibited Aß1-42-induced production and mRNA levels of tumor necrosis factor-α (TNF-α), interleukin 1ß (IL-1ß), and interleukin 6 (IL-6). Engeletin enhanced Aß1-42-induced activation of Kelch-like ECH-associated protein 1 (Keap1)/nuclear transcription factor E2-related factor 2 (Nrf2) signaling pathway in BV-2 cells. Inhibition of Keap1/Nrf2 signaling pathway reversed the inhibitory effects of engeletin on Aß1-42-induced oxidative stress and inflammation in BV-2 cells. Taken together, engeletin attenuated Aß1-42-induced oxidative stress and inflammation in BV-2 cells via regulating the of Keap1/Nrf2 pathway. These findings indicated that engeletin might be served as a therapeutic agent for the treatment of AD.

MiR-876-3p targets KIF20A to block JAK2/STAT3 pathway in glioma.

Aberrant expression of miRNAs has been reported to be involved in the development and progression of glioma. But the function of miR-876-3p in glioma is unknown. We found that miR-876-3p is significantly downregulated in glioma tissues and cell lines. Overexpression of miR-876-3p suppressed glioma cell proliferation, epithelial-mesenchymal transition, migration, and invasion. By prediction combining with luciferase reporter assay, we identified that miR-876-3p could decrease the expression of KIF20A by directly targeting the region of its 3'UTR. Furthermore, we observed that overexpression of miR-876-3p inhibited the expression of KIF20A, thus blocking the protein kinase JAK2/STAT3 pathway. Overexpressed KIF20A reversed miR-876-3p-induced suppression of glioma cell proliferation, migration, and invasion. We also demonstrated the inhibitory effect of miR-876-3p on tumor growth in glioma using an in vivo model. The miR-876-3p/KIF20A-axis mediated JAK2/STAT3 pathway have therapeutic potential in glioma treatment.

Serum Soluble Corin Deficiency Predicts Major Disability within 3 Months after Acute Stroke.

OBJECTIVE: Serum soluble corin has been associated with stroke. However, whether it is associated with stroke prognosis has not yet been studied. Therefore, we aimed to study the association of serum soluble corin with risk of poor outcomes within 3 months after stroke. METHODS: We followed 522 stroke patients for 3 months to identify major disability, death and vascular events. Serum soluble corin was measured at baseline for all participants. Logistic regression was used to examine the associations of baseline serum soluble corin with outcomes of stroke, adjusting for age, sex, baseline NIHSS score, hours from onset to hospitalization, smoking, drinking, hypertension, diabetes, coronary heart disease, atrial fibrillation, family history of stroke, and stroke subtype. RESULTS: Patients with high corin had a significantly lower crude risk for the composite outcome of major disability or death (OR = 0.64, 95%CI: 0.43-0.96) than patients with low corin (the lowest tertile). After adjustment for age and baseline NIHSS score, patients with high corin still had a significantly lower risk for the composite outcome of major disability or death (OR = 0.60, 95%CI: 0.36-0.99). This association became bottom line significant after additionally adjusting for other conventional factors (OR = 0.61, P = 0.058). No association was found between serum soluble corin and other composite outcomes. CONCLUSION: Serum soluble corin deficiency predicted risk for major disability within 3 months after stroke, independent of baseline neurological deficient. Our results may indicate a probable role of corin in stroke prognosis.